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Hae Won Lee,1,2 Woo Youl Kang,1,2 Wookjae Jung,1,2 Mi-Ri Gwon,1,2 Kyunghee Cho,3 Young-Ran Yoon,1,2 Sook Jin Seong1,2 1Department of Molecular Medicine, School of Medicine, Kyungpook National University, Daegu, 41944, Republic of Korea; 2Department of Clinical Pharmacology, Kyungpook National University Hospital, Daegu, 41944, Republic of Korea; 3Analytical Research Division, Biocore Co. Ltd., Seoul, 08511, Republic of KoreaCorrespondence: Young-Ran Yoon, Department of Molecular Medicine, School of Medicine, Kyungpook National University, 130 Dongdeok-Ro, Jung-gu, Daegu, 41944, Republic of Korea, Tel +82 53-420-4950, Fax +82 53-420-5218, Email yry@knu.ac.kr Sook Jin Seong, Department of Clinical Pharmacology, School of Medicine, Kyungpook National University, 130 Dongduk-Ro, Jung-gu, Daegu, 41944, Republic of Korea, Tel +82 53-200-6351, Fax +82 53-420-5218, Email wintersj@knu.ac.krBackground: YYD601 was developed as a novel dual delayed release (DDR) formulation of esomeprazole to prolong the plasma esomeprazole concentration and extend the duration of acid suppression.Purpose: The pharmacokinetic (PK) and pharmacodynamics (PD) characteristics of YYD601 after single and multiple oral administrations were investigated in healthy Korean adults under fasting and fed conditions, and compared with the original esomeprazole capsule.Methods: In the single-center, randomized, open-label, parallel-design, two-period study, thirty two volunteers were enrolled into four dosing groups, including esomeprazole 40-mg (group A), YYD60130-mg (group B), YYD601 40-mg (group C), and YYD601 60-mg (group D) once daily for 5 days. Blood samples were collected for PK analysis, before and up to 24 h after dosing. For PD characteristics of YYD601, the percentages of time with intragastric pH > 4 over a 24-h period and during night-time following multiple oral administrations were evaluated.Results: A total of 27 subjects completed the study. YYD601 showed a dual-peak PK profile under fasting condition, with delayed Tmax, compared with conventional formulation. There were no significant differences in the AUC values adjusted for dose between the three YYD601 dosage groups and the conventional esomeprazole 40 mg. The esomeprazole AUC following single and multiple administration decreased with food intake by approximately 33%. YYD601 showed a linear pharmacokinetic profile in the dose range studied. There was no statistically significant difference in increase in mean percentage of time with intragastric pH > 4 for 24-hour and during night-time between the three different doses of YYD601 and the conventional formulation. The treatments were well-tolerated during the study and no serious adverse events were observed.Conclusion: YYD601 30 mg has a comparable effect on gastric acid inhibition as conventional esomeprazole 40 mg following once daily oral administration. Single and multiple oral dosing of YYD601 up to 60 mg were safe and well-tolerated throughout the study.Clinical Trial Registry: http://clinicaltrials.gov, NCT03558477 (date of registration: June 15, 2018; study period: between October 2017 and February 2018).Keywords: esomeprazole, dual delayed release, pharmacokinetics, pharmacodynamics

Woo Youl Kang,1,2,* Hae Won Lee,1,2,* Mi-Ri Gwon,1,2 Seungil Cho,1,2 Wang-Seob Shim,3 Kyung-Tae Lee,3 Dong Heon Yang,4 Sook Jin Seong,1,2 Young-Ran Yoon1,2 1Department of Molecular Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea; 2Department of Clinical Pharmacology, Kyungpook National University Hospital, Daegu, Republic of Korea; 3Kyung Hee Drug Analysis Center, Kyung Hee University, Seoul, Republic of Korea; 4Division of Cardiology, Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea*These authors contributed equally to this workCorrespondence: Young-Ran YoonDepartment of Molecular Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of KoreaTel +82-53-420-4950Fax +82-53-420-5218Email yry@knu.ac.krSook Jin SeongDepartment of Clinical Pharmacology, Kyungpook National University Hospital, Daegu, Republic of KoreaTel +82-53-200-6351Fax +82-53-420-5218Email wintersj@knu.ac.krObjective: Fimasartan, an angiotensin II type 1 receptor blocker, and linagliptin, a dipeptidyl-peptidase-4 inhibitor, are frequently coadministered to treat patients with hypertension and diabetes, respectively. This study sought to evaluate the pharmacokinetic interactions between fimasartan and linagliptin after co-administration in healthy Korean subjects.Methods: The overall study was divided into two separate parts, with each part designed as an open-label, multiple-dose, two-period, and single-sequence study. In Part A, to investigate the effect of linagliptin on fimasartan, 25 subjects received 120 mg fimasartan alone once daily for seven days during Period I, and 120 mg fimasartan with 20 mg linagliptin for seven days during Period II. In Part B, to examine the effect of fimasartan on linagliptin, 12 subjects received only linagliptin once daily for seven days during Period I, followed by concomitant administration of fimasartan for seven days during Period II, at the same doses used in Part A. Serial blood samples were collected at scheduled intervals for up to 24 h after the last dose to determine the steady-state pharmacokinetics of both drugs.Results: Thirty-six subjects completed the study. The geometric mean ratio and 90% confidence intervals for maximum plasma concentration at steady state (Cmax,ss) and area under the concentration–time curve at steady state (AUCτ,ss) of fimasartan with or without linagliptin were 1.2633 (0.9175– 1.7396) and 1.1740 (1.0499– 1.3126), respectively. The corresponding values for Cmax,ss and AUCτ,ss of linagliptin with or without fimasartan were 0.9804 (0.8480– 1.1336) and 0.9950 (0.9322– 1.0619), respectively. A total of eight adverse events (AEs) were reported and the incidence of AEs did not increase significantly with co-administration of the drugs.Conclusion: Our results suggest that there are no clinically significant pharmacokinetic interactions between fimasartan and linagliptin when co-administered. Treatments were well tolerated during the study, with no serious adverse effects.Clinical Trial Registry: http://clinicaltrials.gov, NCT03250052.Keywords: fimasartan, pharmacokinetics, drug–drug interaction, linagliptin, safety

Hae Won Lee*,1,2, Sook Jin Seong*,1,2, Woo Youl Kang1,2, Boram Ohk1,2, Mi-Ri Gwon1,2, Bo Kyung Kim1,2, Seungil Cho1,2, Kyunghee Cho3, Yong Kyung Sung4, Young-Ran Yoon1,2, Jong Gwang Kim5 1Department of Molecular Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea; 2Department of Clinical Pharmacology, Kyungpook National University Hospital, Daegu, Republic of Korea; 3Analytical Research Division, Biocore Co. Ltd., Seoul, Republic of Korea; 4Department of R&D, Myungmoon Pharm. Co., Ltd., Seoul, Republic of Korea; 5Department of Oncology/Hematology, Kyungpook National University Hospital, Kyungpook National University School of Medicine, Kyungpook National University Cancer Research Institute, Kyungpook National University, Daegu, Republic of Korea*These authors contributed equally to this workCorrespondence: Young-Ran YoonDepartment of Molecular Medicine, School of Medicine, Kyungpook National University, 130 Dongduk-Ro, Jung-gu, Daegu 41944, Republic of KoreaTel +82 53 420 4950Fax +82 53 426 4944Email yry@knu.ac.krJong Gwang KimDepartment of Oncology/Hematology, Kyungpook National University Hospital, Kyungpook National University School of Medicine, Kyungpook National University Cancer Research Institute, Kyungpook National University, 130 Dongduk-Ro, Jung-gu, Daegu 41944, Republic of KoreaTel +82 53 200 6522Fax +82 53 420 5218Email jkk21c@knu.ac.krPurpose: S-1 is an oral fluoropyrimidine anticancer drug consisting of the 5-fluorouracil prodrug tegafur combined with gimeracil and oteracil. The purpose of this study was to evaluate the pharmacokinetic (PK), bioequivalence, and safety of a newly developed generic formulation of S-1 compared with the branded reference formulation, in Korean gastric cancer patients.Methods: This was a single-center, randomized, open-label, single-dose, two-treatment, two-way crossover study. Eligible subjects were randomly assigned in a 1:1 ratio to receive the test formulation or reference formulation, followed by a one-week washout period and administration of the alternate formulation. Serial blood samples were collected at 0 hrs (predose), 0.25, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hrs after dosing in each period. The plasma concentrations of tegafur, 5-FU, gimeracil, and oteracil were analyzed using a validated liquid chromatography-tandem mass spectrometry method. The PK parameters were calculated using a non-compartmental method.Results: In total, 29 subjects completed the study. All of the 90% confidence intervals (CIs) of the geometric mean ratios (GMRs) fell within the predetermined acceptance range. No serious adverse events were reported during the study.Conclusion: The new S-1 formulation met the Korean regulatory requirement for bioequivalence. Both S-1 formulations were well tolerated in all subjects.Clinical trial registry: https://cris.nih.go.kr CRIS KCT0003855.Keywords: S-1, pharmacokinetics, bioequivalence, tegafur, gimeracil, oteracil

Woo Youl Kang,1,2,* Sook Jin Seong,1,2,* Boram Ohk,1,2 Mi-Ri Gwon,1,2 Bo Kyung Kim,1,2 Seungil Cho,1,2 Wang-Seob Shim,3 Kyung-Tae Lee,4 Eun Hee Kim,5 Dong Heon Yang,6 Hae Won Lee,1,2 Young-Ran Yoon1,2 1Department of Molecular Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea; 2Department of Clinical Pharmacology, Kyungpook National University Hospital, Daegu, Republic of Korea; 3Kyung Hee Drug Analysis Center, Kyung Hee University, Seoul, Republic of Korea; 4College of Pharmacy, Kyung Hee University, Seoul, Republic of Korea; 5College of Nursing, Catholic University of Daegu, Gyeongsan-si, Gyeongbuk, Republic of Korea; 6Division of Cardiology, Department of Internal Medicine, Kyungpook National University Hospital, Daegu, Republic of Korea *These authors contributed equally to this work Purpose: A new fixed-dose combination (FDC) formulation of 120 mg fimasartan and 20 mg rosuvastatin was developed to increase therapeutic convenience and improve treatment compliance. Methods: A randomized, open-label, single-dose, two-treatment, two-way crossover study with a 7-day washout period was conducted to compare the pharmacokinetic (PK) characteristics and bioequivalence between an FDC of fimasartan/rosuvastatin and the separate co-administration of fimasartan and rosuvastatin in healthy Korean volunteers. The plasma concentrations of fimasartan and rosuvastatin were analyzed by a validated liquid chromatography-tandem mass spectrometry method, for which serial blood samples were collected for up to 48 hours post-administration of fimasartan and 72 hours post-administration of rosuvastatin, in each period. The PK parameters were calculated using a non-compartmental method. Results: A total of 78 subjects completed the study. All the 90% CIs of the geometric mean ratios (GMRs) fell within the predetermined acceptance range. The GMR and 90% CI for the area under the plasma concentration-time curve from time 0 to the last measurement (AUC0–t) and the maximum plasma concentration (Cmax) for fimasartan were 0.9999 (0.9391–1.0646) and 1.0399 (0.8665–1.2479), respectively. The GMR and 90% CI for the AUC0–t and Cmax for rosuvastatin were 1.0075 (0.9468–1.0722) and 1.0856 (0.9944–1.1852), respectively. Treatment with fimasartan and rosuvastatin was generally well tolerated without serious adverse events. Conclusion: The new FDC formulation of 120 mg fimasartan and 20 mg rosuvastatin can be substituted for the separate co-administration of fimasartan and rosuvastatin, for the advantage of better compliance with convenient therapeutic administration. Keywords: fixed-dose combination, pharmacokinetics, bioequivalence, fimasartan, rosuvastatin

Woo Youl Kang,1,2,* Sook Jin Seong,1,* Boram Ohk,1,2 Mi-Ri Gwon,1,3 Bo Kyung Kim,1,2 Sookie La,4 Hyun-Ju Kim,3 Seungil Cho,1 Young-Ran Yoon,1,2 Dong Heon Yang,5 Hae Won Lee1 1Clinical Trial Center, Kyungpook National University Hospital, Daegu, Republic of Korea; 2Department of Biomedical Science, BK21 Plus KNU Bio-Medical Convergence Program for Creative Talent, Kyungpook National University Graduate School, Daegu, Republic of Korea; 3Department of Molecular Medicine, Cell and Matrix Research Institute, Kyungpook National University School of Medicine, Daegu, Republic of Korea; 4Analytical Research Division, Biocore Co Ltd, Seoul, Republic of Korea; 5Division of Cardiology, Department of Internal Medicine, Kyungpook National University School of Medicine & Hospital, Daegu, Republic of Korea *These authors contributed equally to this work Purpose: A new fixed-dose combination (FDC) formulation of telmisartan 80 mg and S-amlodipine 5 mg (CKD-828) has been developed to increase convenience (as only one tablet is required per day) and improve treatment compliance.Methods: The pharmacokinetic characteristics and tolerability of an FDC of telmisartan and S-amlodipine were compared to those after coadministration of the individual agents in this randomized, open-label, single-dose, two-way, four-period, crossover study. To analyze the telmisartan and S-amlodipine plasma concentrations using a validated liquid chromatography–tandem mass spectrometry method, serial blood samples were collected up to 48 hours post-dose for telmisartan and 144 hours post-dose for S-amlodipine, in each period.Results: Forty-eight healthy subjects were enrolled, and 43 completed the study. The mean peak plasma concentration (Cmax) and the area under the plasma concentration–time curve from time 0 to the last measurement (AUC0–t) values of telmisartan were 522.29 ng/mL and 2,475.16 ng⋅h/mL for the FDC, and 540.45 ng/mL and 2,559.57 ng⋅h/mL for the individual agents concomitantly administered, respectively. The mean Cmax and AUC0–t values of S-amlodipine were 2.71 ng/mL and 130.69 ng⋅h/mL for the FDC, and 2.74 ng/mL and 129.81 ng⋅h/mL for the individual agents concomitantly administered, respectively. The geometric mean ratio (GMR) and 90% confidence interval (CI) for the telmisartan Cmax and AUC0–t (FDC of telmisartan and S-amlodipine/concomitant administration) were 0.8509 (0.7353–0.9846) and 0.9431 (0.8698–1.0226), respectively. The GMR and 90% CI for the S-amlodipine Cmax and AUC0–t (FDC/concomitant administration) were 0.9829 (0.9143–1.0567) and 0.9632 (0.8798–1.0546), respectively. As the intrasubject variability of the Cmax for telmisartan administered individually was 42.94%, all 90% CIs of the GMRs fell within the predetermined acceptance range. Both treatments were well tolerated in this study. Conclusion: CKD-828 FDC tablets were shown to be bioequivalent to coadministration of the individual agents with the respective strength, in healthy subjects under fasting conditions. There was no significant difference in safety profile between the two treatments. Keywords: fixed-dose combination, pharmacokinetics, S-amlodipine, telmisartan, safety

Hae Won Lee,1,* Sook Jin Seong,1,* Boram Ohk,1,2 Woo Youl Kang,1,2 Mi-Ri Gwon,1 Bo Kyung Kim,1,2 Hyun-Ju Kim,3 Young-Ran Yoon1,2 1Clinical Trial Center, Kyungpook National University Hospital, 2Department of Biomedical Science, BK21 Plus KNU Bio-Medical Convergence Program for Creative Talent, Kyungpook National University Graduate School, 3Cell and Matrix Research Institute, Daegu, Republic of Korea *These authors contributed equally to this work Objective: This study evaluated the pharmacokinetics (PKs) and safety of a newly developed β-lapachone (MB12066) tablet, a natural NAD(P)H:quinone oxidoreductase 1 (NQO1) substrate, in healthy male volunteers.Methods: In a randomized, double-blind, multiple-dose, two-treatment study, 100 mg MB12066 or placebo was given twice daily for 8 days to groups of eight or three fasted healthy male subjects, respectively, followed by serial blood sampling. Plasma concentrations for β-lapachone were determined using liquid chromatography–tandem mass spectrometry. PK parameters were obtained with non-compartmental analysis. Tolerability was assessed based on physical examinations, vital signs, clinical laboratory tests, and electrocardiograms.Results: Following a single 100 mg MB12066 oral dose, maximum plasma concentration (Cmax) of β-lapachone was 3.56±1.55 ng/mL, and the median (range) time to reach Cmax was 3 h (2–5 h). After the 8 days of 100 mg twice daily repeated dosing was completed, mean terminal half-life was determined to be 18.16±3.14 h, and the mean area under the plasma concentration vs time curve at steady state was 50.44±29.68 ng·h/mL. Accumulation index was 2.72±0.37. No serious adverse events (AEs) were reported, and all reported intensities of AEs were mild.Conclusion: The results demonstrated that MB12066 was safe and well tolerated in healthy volunteers and that there were no serious AEs. Accumulation in plasma with twice-daily administration was associated with a 2.72 accumulation ratio. Keywords: β-lapachone, healthy volunteers, MB12066, pharmacokinetics, safety

Objective: To analyze pregnancy outcomes in young women with stage IA, grade 1 endometrioid adenocarcinoma of the uterus after successful fertility-sparing management using progestin.Methods: We reviewed the medical records of 141 women with stage IA, grade 1 endometrioid adenocarcinoma of the uterus who had complete remission after progestin treatment. Statistical analysis was performed using Student's t test or Mann-Whitney U test for continuous variables, using χ or Fisher's exact test for categorical variables, and using log-rank test for survival comparison.Results: Fifty-four (38.3%) women in the study cohort had a history of infertility. Seventy (49.6%) of the 141 patients tried to conceive with 44 (62.9%) receiving fertility drugs. The median interval to attempted pregnancy after treatment was 5 months (range 1-31 months). The median age at the time of the pregnancy trial was 32.4 years (range 23-40 years). Fifty-one (73%) of 70 women who tried to conceive were successful and 46 (66%) gave birth to 58 live neonates. The spontaneous abortion rate, ectopic pregnancy rate, and preterm delivery rates in our cohort were 24%, 2.8%, and 11.5%, respectively. The 5-year disease-free survival was similar between patients who received fertility drugs (n=44) or who did not (n=97) (73% compared with 62%, P=.335), and this rate was significantly higher in patients who achieved at least one pregnancy (n=51) than those who did not (n=90) (76% compared with 62%, P=.028).Conclusions: Although the proportion of patients with a history of subfertility or infertility was high in our cohort, the pregnancy outcomes were very promising using assisted reproductive technology. The use of fertility drugs was not associated with a higher incidence of cancer recurrence after successful fertility-sparing management in this study population.Level Of Evidence: II. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to investigate the association between blood levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and cognitive impairments among elderly individuals., Methods: Peripheral concentration of TNF-α and IL-6 were measured in all subjects. To assess individual cognitive function, the Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Assessment Battery (CERAD-NP) was used, and standardized scores (z-scores) were calculated for each test. Cytokine levels were compared between the diagnostic groups, and correlations between blood inflammatory factor levels and z-scores were analyzed., Results: The 37 participants included 8 patients with Alzheimer's disease (AD), 15 subjects with mild cognitive impairment (MCI), and 14 cognitively healthy controls. TNF-α and IL-6 levels were higher in patients with AD than in healthy controls. TNF-α levels were higher in the AD group than in the MCI group. However, after adjusting for age, the associations between diagnosis and TNF-α and IL-6 were not significant. The higher the plasma IL-6 level, the lower the z-scores on the Boston Naming Test, Word List Learning, Word List Recognition, and Constructional Recall. The higher the serum TNF-α level, the lower the z-scores on the Word List Learning and Constructional Recall. Negative correlation between serum TNF-α level and the z-score on Word List Learning remained significant when age was adjusted., Conclusion: The difference in the blood levels of TNF-α and IL-6 between the diagnostic groups may be associated with aging. However, elevated TNF-α levels were associated with worse immediate memory performance, even after adjusting for age.

Objective: This study investigated to what extent a range of depressive symptoms was differentially present depending on age group in Korean population., Methods: Data was pooled from five nationally representative surveys in which 29,418 respondents aged at least 18 years were interviewed face-to-face using the Korean version of the Composite International Diagnostic Interview. A total of 691 (2.1%) respondents were found to have had at least 1 episode of major depressive disorder (MDD) within the last 12 months. Logistic regression analysis was conducted to identify the association between age groups (18-39 years, 40-59 years, and 60 years or older) and 26 depressive symptoms among the respondents with MDD., Results: Associations were observed between somatic symptoms-including insomnia, awakening 2 h earlier-and cognitive symptoms such as feelings of guilt, thoughts of death, and suicidal ideation with the older age group. Whereas, atypical depressive symptoms such as increased appetite, weight gain, and hypersomnia were associated with the younger age group. When adjusted for sociodemographic factors, symptoms such as depressed mood, awakening 2 h earlier, and feeling guilty in the older age group, and hypersomnia, psychomotor retardation, and worse in the morning in the younger age group still remained statistically significant. Furthermore, fatigue and decreased libido were newly associated with the younger age group., Conclusion: The findings of this study revealed distinct patterns of symptomatology in MDD based on age groups. These differences should be considered owing to their potential relevance to treatment response and prognosis in the clinical setting.

Objective: To identify the effects of subcutaneous drain insertion on wound dehiscence and infection in patients who underwent gynecological midline laparotomy., Methods: This analysis identified the secondary endpoints of the KGOG 4001 study, a prospective, multicenter, non-blind, randomized controlled trial. Patients scheduled to undergo midline laparotomy for gynecological diseases and, with body mass index<35 kg/m 2 , were randomized (1:1) to treatment (with subcutaneous drain) and control (without subcutaneous drain) groups from February 2021 to December 2021. We compared the incidence rate of wound dehiscence 4 weeks post-surgery and the cumulative incidence rate of wound dehiscence and infection up to 4 weeks post-surgery between the two groups., Results: Of 174 patients randomized to the treatment (n = 84) and control (n = 90) groups, 12 were excluded owing to loss to follow-up; finally, 162 patients (treatment, n = 79; control, n = 83) were included in intention-to-treat analysis. The frequency of cancer surgery (79.7 % vs. 77.1 %, p = 0.683), mean surgery time (227.7 vs. 226.7 min, p = 0.960), and mean wound length (24.2 vs. 24.3 cm, p = 0.933) were comparable between two groups. No significant differences were observed in the incidence rate of wound dehiscence 4 weeks post-surgery (1.3 % vs. 2.4 %, p > 0.999), cumulative incidence rate of wound dehiscence (8.9 % vs. 6.0 %, p = 0.491), and cumulative incidence rate of wound infection (1.3 % vs. 0.0 %, p = 0.488) up to 4 weeks post-surgery between the two groups., Conclusion: Subcutaneous drain insertion is not associated with a significant improvement in the incidence of wound dehiscence and infection in patients who undergo gynecological midline laparotomy., Clinical Trial Registration: ClinicalTrials.gov, NCT04643197., Competing Interests: Declaration of competing interest Kidong Kim reports grants from Ethicon, Inc.- Johnson and Johnson MedTech during the conduct of the study. All other authors have no conflicts of interest to disclose., (Copyright © 2024 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

In this study, we aimed to demonstrate the feasibility and safety of navigating the ureters, middle sacral artery (MSA), and superior hypogastric nerve (SHN) using indocyanine green (ICG) and near-infrared fluorescence (NIRF) imaging during robot-assisted sacrocolpopexy (RSCP). Overall, 15 patients who underwent RSCP for apical vaginal prolapse were retrospectively enrolled. All patients underwent cystoscopic intraureteric instillation of 5 cc ICG (2.5 mg/mL) before RSCP and intravenous injection of 3 cc ICG during presacral dissection and mesh fixation. In all patients, the fluorescent right ureter was clearly identified in real time. The MSA was visualized on ICG-NIRF images in 80% (13/15) of patients. The mean time from ICG injection to MSA visualization was 43.7 s; the mean duration of the arterial phase was 104.3 s. Fluorescent SHN was detected in 73.3% (11/15) of patients. The time from ICG injection to SHN fluorescence was 48.4 s; the duration of fluorescence was 177.2 s. There was no transfusion, iatrogenic ureteral injury, or bowel or urinary dysfunction. Our results indicated that intraoperative ureter, MSA, and SHN mapping using ICG-NIRF images during RSCP is a valuable and safe technique to avoid iatrogenic ureteral, vascular, and neural injuries and to simplify surgical procedures. Nonetheless, further studies are required.

Background: ArtiSential, a class of innovative laparoscopic instrument, has been developed to overcome the limitations of conventional laparoscopic surgery by enabling free, 360°-unrestricted movement of the wrist joint, as in robotic surgery., Objective: The aim of the present study was to describe the initial experiences with these devices in myomectomy and to report the surgical outcomes., Methods: A total of 77 women undergoing laparoscopic or robotic myomectomy between January 2021 and June 2022 were included in this multicenter prospective study. The ArtiSential instruments used by the surgeons were those chosen according to their respective preferences. The baseline characteristics, surgical outcomes, trocar placement options, and operator survey results were scrutinized., Results: The mean age of the patients was 39.9 ± 6.3, and the mean body mass index (BMI, calculated as weight in kilograms divided by the square of height in meters) was 22.4 ± 3.4 kg/m 2 ; 46.8% of the patients underwent robotic surgery, while 53.2% underwent laparoscopic surgery. The number of removed myomas was 3.3 ± 3.0, the size of the largest myoma was 7.1 ± 2.3 cm, and the operative time was 130.0 ± 54.0 min. No transfusions or laparotomy conversions were required. Other than one case of ileus, there were no postoperative complications. In most cases, the instruments were inserted through the umbilicus trocar, and the fenestrated forceps, needle holder, and bipolar fenestrated forceps, in that order, were frequently employed. According to a surgeon survey, 29.9% moderately or strongly agreed that the ArtiSential devices utilized were more convenient than conventional laparoscopic instruments, while only 9.7% moderately or strongly agreed that they were more convenient than robotic instruments., Conclusions: Myomectomy as performed with an ArtiSential instrument seems to be feasible and safe. Further studies are necessary in order to comparatively assess the outcomes and potential benefits of ArtiSential, robotic, and conventional laparoscopic myomectomy., (© 2024 International Federation of Gynecology and Obstetrics.)

Purpose: Robotic single-site plus one-port myomectomy (RSOM) was designed to reduce the number of incision sites for greater cosmetic satisfaction of patients while retaining the benefits of conventional robotic multi-site myomectomy (CRM). Robotic single-site plus two-port myomectomy (RSTM) eliminated one port relative to conventional CRM, and RSOM achieved the same advantage with respect to RSTM. This study aimed to compare RSOM with RSTM in terms of their respective methodologies and surgical outcomes., Materials and Methods: The medical records of 230 patients who had undergone RSOM and 146 patients who had undergone RSTM were reviewed. The groups' surgical outcomes were compared using propensity score matching (PSM) analysis., Results: In the total data, RSOM had a shorter operative time (135.1±57.4 min vs. 149.9±46.2 min, p =0.009) and a shorter hospital stay (5.2±0.5 days vs. 5.4±0.7 days, p =0.033) relative to RSTM. The PSM analysis showed that there were no statistically significant intergroup differences in the patients' baseline characteristics. Regarding the surgical outcomes, the RSOM group showed shorter operative time (129.2±49.3 min vs. 148.7±46.3 min, p =0.001) compared to the RSTM group., Conclusion: Compared with RSTM, RSOM was associated with shorter operative time. Additionally, more detailed comparative and prospective studies are needed to evaluate RSOM relative to RSTM., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2024.)

Objectives: Fertility-sparing treatment (FST) might be considered an option for reproductive patients with low-risk endometrial cancer (EC). On the other hand, the matching rates between preoperative assessment and postoperative pathology in low-risk EC patients are not high enough. We aimed to predict the postoperative pathology depending on preoperative myometrial invasion (MI) and grade in low-risk EC patients to help extend the current criteria for FST., Methods/materials: This ancillary study (KGOG 2015S) of Korean Gynecologic Oncology Group 2015, a prospective, multicenter study included patients with no MI or MI <1/2 on preoperative MRI and endometrioid adenocarcinoma and grade 1 or 2 on endometrial biopsy. Among the eligible patients, Groups 1-4 were defined with no MI and grade 1, no MI and grade 2, MI <1/2 and grade 1, and MI <1/2 and grade 2, respectively. New prediction models using machine learning were developed., Results: Among 251 eligible patients, Groups 1-4 included 106, 41, 74, and 30 patients, respectively. The new prediction models showed superior prediction values to those from conventional analysis. In the new prediction models, the best NPV, sensitivity, and AUC of preoperative each group to predict postoperative each group were as follows: 87.2%, 71.6%, and 0.732 (Group 1); 97.6%, 78.6%, and 0.656 (Group 2); 71.3%, 78.6% and 0.588 (Group 3); 91.8%, 64.9%, and 0.676% (Group 4)., Conclusions: In low-risk EC patients, the prediction of postoperative pathology was ineffective, but the new prediction models provided a better prediction., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Jang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: There are many studies regarding the increased relationship between pregnancy outcomes of singleton with endometriosis. However, there was limited evidence of twin pregnancies with endometriosis. This study aimed to compare the pregnancy outcomes and complications in twin pregnancies with or without endometriosis in a single institution., Materials and Methods: From January 2011 to July 2022, a retrospective analysis of twin pregnancies was conducted. The endometriosis group included patient with histological or visual confirmation before pregnancy or during cesarean section. Pregnancy outcomes and complications were compared between the two groups., Results: Out of 1714 patients examined, 127 (7.4%) were included in the endometriosis group. Maternal body mass index (BMI) was lower in the endometriosis group ( p <0.001). There were no significant differences in maternal age, mode of conception, chorionicity, and pregnancy outcomes, such as gestational age at delivery ( p =0.835) and the preterm birth rate ( p =0.579). The endometriosis group had a significantly higher rate of obstetrical complication: small for gestational age (SGA) <10% ( p =0.029). However, after adjustment for BMI, the endometriosis group showed no statistical significance in obstetrical complications, including SGA (adjusted odds ratio, 1.568; 95% confidence interval, 0.984-2.499; p =0.059)., Conclusion: Twin pregnancies with endometriosis were not related to adverse effects on pregnancy outcomes and obstetrical complications. To confirm these outcomes, further large prospective studies are required., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2024.)

Objectives: This study aimed to evaluate the clinical efficacy of fertility-preserving therapy through in vitro fertilization (IVF) procedures in women who were pathologically diagnosed with endometrial hyperplasia or carcinoma., Design: A retrospective cohort study on fertility-preserving therapy was conducted. Participants/Materials, Setting: A total of 82 women were enrolled who had simple endometrial hyperplasia (SH), complex hyperplasia (CH), complex atypical hyperplasia (CAH), and endometrioid endometrial carcinoma stage IA (EC IA) and underwent IVF at Gangnam CHA fertility center between January 2008 and December 2020., Methods: The primary endpoints were oncologic outcomes and subsequent reproductive outcomes of patients who underwent fertility-preserving treatments analyzed by χ2 test or Fisher's exact test., Results: Of the 82 patients, 33 had a cumulative clinical pregnancy (40.2%), and 25 had a cumulative live birth (30.5%) through IVF procedures following pathologic confirmation of complete remission or non-progressive status. The cumulative clinical pregnancy rates and live birth rates for SH were 50.0% and 30.0%, for CH were 37.8% and 28.9%, for CAH were 25.0% and 25.0%, and for EC were 38.5% and 38.5%, respectively. There were no significant differences in cumulative clinical pregnancy rates or live birth rates when comparing the four groups. There was a difference in endometrial thickness between medroxyprogesterone acetate (MPA) treatment group and intrauterine device (IUD) group (p = 0.036); however, there were no significant differences in clinical pregnancy rates among MPA, IUD, and MPA+IUD groups., Limitations: Because of the retrospective nature of the study, many factors relevant to the treatment decision were not strictly controlled., Conclusions: All endometrial hyperplasia and carcinoma groups had competent cumulative live birth rates by IVF procedures. There may be differences in endometrial thickness depending on the treatment methods, but this does not affect clinical pregnancy rates. Therefore, the fertility-preserving treatment for endometrial hyperplasia and carcinoma is a safe and feasible method that results in good IVF outcomes., (© 2024 S. Karger AG, Basel.)

Objective: We aimed to predict the risk of postoperative adjuvant therapy using preoperative variables in young patients with early stage cervical cancer. The predicted risk can guide whether ovarian transposition should be performed during surgery., Methods: In total, 886 patients with stage IB1-IIA cervical cancer aged 20-45 years who underwent modified radical or radical hysterectomy between January 2000 and December 2008 were included. Preoperative variables, preoperative laboratory findings, International Federation of Gynaecology and Obstetrics stage, tumor size, and pathological variables were collected. Patients with high risk factors or those who met the Sedlis criteria were considered adjuvant therapy risk (+); others were considered adjuvant therapy risk (-). A decision-tree model using preoperative variables was constructed to predict the risk of adjuvant therapy., Results: Of 886 patients, 362 were adjuvant therapy risk (+) (40.9%). The decision-tree model with four distinct adjuvant therapy risks using tumor size and age were generated. Specifically, patients with tumor size ≤2.45 cm had low risk (49/367; 13.4%), those with tumor size ≤3.85 cm and >2.45 cm had moderate risk (136/314; 43.3%), those with tumor size >3.85 cm and age ≤39.5 years had high risk (92/109; 84.4%), and those with tumor size >3.85 cm and age >39.5 years had the highest risk (85/96; 88.5%)., Conclusion: The risk of postoperative adjuvant therapy in young patients with early stage cervical cancer can be predicted using preoperative variables. We can decide whether ovarian transposition should be performed using the predicted risk.

Soft tissue sarcoma (STS) is a relatively rare malignancy, accounting for about 1% of all adult cancers. It is known to have more than 70 subtypes. Its rarity, coupled with its various subtypes, makes early diagnosis challenging. The current standard treatment for STS is surgical removal. To identify the prognosis and pathophysiology of STS, we conducted untargeted metabolic profiling on pre-operative and post-operative plasma samples from 24 STS patients who underwent surgical tumor removal. Profiling was conducted using ultra-high-performance liquid chromatography-quadrupole time-of-flight/mass spectrometry. Thirty-nine putative metabolites, including phospholipids and acyl-carnitines were identified, indicating changes in lipid metabolism. Phospholipids exhibited an increase in the post-operative samples, while acyl-carnitines showed a decrease. Notably, the levels of pre-operative lysophosphatidylcholine (LPC) O-18:0 and LPC O-16:2 were significantly lower in patients who experienced recurrence after surgery compared to those who did not. Metabolic profiling may identify aggressive tumors that are susceptible to lipid synthase inhibitors. We believe that these findings could contribute to the elucidation of the pathophysiology of STS and the development of further metabolic studies in this rare malignancy., Competing Interests: The authors declare no conflicts of interest.

Background: This study aimed to compare surgical outcomes between two new robotic single-site myomectomy (RSSM)-complementary techniques: coaxial robotic single-site myomectomy (Coaxial-RSSM) and hybrid robotic single-site myomectomy (Hybrid-RSSM)., Methods: Medical records for 132 women undergoing Coaxial-RSSM and 150 undergoing Hybrid-RSSM, consecutively, were retrospectively reviewed. Patient characteristics and surgical outcomes were assessed and compared after propensity score matching (PSM)., Results: In the outcomes of PSM, the Coaxial-RSSM group showed significantly reduced blood loss (79.71 vs. 163.75 mL, p < 0.001) and reduced hospital duration (4.18 ± 0.62 vs. 4.63 ± 0.90) relative to the Hybrid-RSSM group. Conversely, Hybrid-RSSM allowed for a shorter operative time compared with Coaxial-RSSM (119.19 vs. 156.01 min, p = 0.007). No conversions to conventional laparoscopy or laparotomy or any need for the multi-site robotic approach occurred in either group. Postoperative complications, including ileus, fever, and wound dehiscence, showed no statistically significant differences between the two groups., Conclusions: Blood loss was lower with Coaxial-RSSM, and operative time was shorter for Hybrid-RSSM. A follow-up prospective study is warranted for more comprehensive comparison of surgical outcomes between the two techniques.

Objective: To investigate pathologic complete response (pCR) and recurrence outcomes using various progestin treatment strategies in patients with atypical hyperplasia/endometrial intraepithelial neoplasia (AH/EIN)., Methods: Medical records of patients diagnosed with AH/EIN and undergoing follow-up endometrial biopsy after progestin treatment between 2011 and 2020 were retrospectively reviewed. Clinical factors and treatment outcomes were analyzed according to initial progestin treatment (oral progestin [OP], levonorgestrel-releasing intrauterine device [LNG-IUD], and combination), OP dose, and maintenance treatment using Pearson's χ 2 , Fisher's exact test, and Kaplan-Meier analysis., Results: Of 124 patients included, 74, 37, and 13 were in the OP, LNG-IUD, and combination groups, respectively. The pCR rate was 79.8% and recurrence rate was 21.2%. The pCR rates within 3 and 6 months were significantly higher in the OP group than in the LNG-IUD group, but were not significantly different within 12 and 24 months. Recurrence rate was significantly higher in the OP group than in the LNG-IUD group. The pCR rate and recurrence rate had no significant differences between the combination group and the other groups. Excluding the LNG-IUD group, 53 and 34 patients received low- and high-dose OP, respectively. The pCR and recurrence rates were comparable between the low- and high-dose OP groups. Maintenance therapy was significantly associated with lower recurrence rate., Conclusions: Although OP alone achieved more short-term pCR than the other groups, more recurrences occurred after pCR than LNG-IUD alone. High-dose OP as well as combination of OP and LNG-IUD did not increase pCR or reduce recurrence. Maintenance therapy may reduce the recurrence rate after pCR., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

In this study, we examined the difference in the vaginal microbiota of women infected with human papillomavirus (HPV), according to menopausal status. A total of 75 cervicovaginal swab samples from 38 pre- and 37 postmenopausal women with HPV infection were obtained from the Korean HPV cohort. Vaginal microbiota analysis, including microbial diversity and specific bacterial abundances, was performed using 16S rRNA gene sequencing. The mean age of the pre- and postmenopausal women were 29.5 and 55.8 years, respectively (p < 0.0001). Lactobacillus spp. were predominant in both groups; however, a marked decrease was observed in postmenopausal women compared to premenopausal women (44.3% vs. 74.2%). Various anaerobic bacteria also showed a relatively high abundance in the postmenopausal group; Atopobium vagina and Gardnerella vaginalis significantly increased in postmenopausal women. Interestingly, no significant differences in bacterial richness were observed between the two groups. However, significant differences in beta-diversity were observed using the Bray-Curtis (p = 0.001), Generalized UniFrac (p = 0.002), Jensen-Shannon (p = 0.001), and UniFrac algorithms (p = 0.002). Theres results indicate that postmenopausal women with HPV infection exhibited a higher degree of vaginal dysbiosis than premenopausal women. Further, HPV-infected postmenopausal women had increased vaginal microbial diversity, characterized by an increase in anaerobic bacteria and concomitant depletion of Lactobacillus spp., (© 2024. The Author(s).)

Background: Subthreshold posttraumatic stress disorder (PTSD) is a chronic condition, and despite its clinical importance, few studies have been conducted. We investigated the relationship of subthreshold PTSD with various psychiatric disorders and suicidality in a South Korean general population., Method: A total of 5,102 respondents, aged at least 18 years, completed face-to-face interviews using the Korean version of the Composite International Diagnostic Interview and questionnaires for lifetime suicidal ideation, plans, and attempts. Subthreshold PTSD was defined as at least one symptom in each of the three symptom clusters (Criteria B, C, and D) and a symptom duration of ≥ 1 month (Criterion E)., Results: The lifetime prevalence of subthreshold PTSD (2.5%) was higher than that of PTSD (1.5%). After adjusting for sociodemographic factors, subthreshold PTSD was significantly associated with nicotine use disorders, major depressive disorder, obsessive-compulsive disorder (OCD), generalized anxiety disorder, and specific phobia. Among psychiatric disorders, the odds ratio for OCD was notably high. Subthreshold PTSD was associated with increased suicidal ideation (adjusted OR [ AOR ] = 2.90, 95% CI [1.98, 4.26]), suicidal plans ( AOR = 3.58, [1.86, 6.89]), and suicide attempts ( AOR = 3.93, [1.93, 8.01]) after adjusting for sociodemographic factors. When adjusted for sociodemographic factors and psychiatric disorders, suicidal ideation ( AOR = 2.04, [1.34, 3.11]) remained statistically significant., Conclusion: This study found that subthreshold PTSD was associated with various psychiatric disorders and suicidality. Increased attention to the mental health of individuals with subthreshold PTSD is necessary. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Raloxifene hydrochloride shows poor bioavailability (only 2%) when orally administered because of its poor aqueous solubility and its extensive first-pass metabolism. A new micronized formulation of raloxifene was developed to improve bioavailability via enhanced gastrointestinal absorption. The primary objective of this study was to evaluate the pharmacokinetic characteristics of a new micronized raloxifene formulation (AD-101) in comparison with the conventional raloxifene formulation. This study was designed as an open-label, randomized, 2-treatment-period, crossover study with a 2-week washout period. Two treatments consisted of micronized raloxifene 45 mg daily; and conventional raloxifene 60 mg daily administered in fasting conditions. Plasma raloxifene concentrations were determined by a validated method using ultra-fast liquid chromatography-tandem mass spectrometry, and pharmacokinetic parameters were calculated using a noncompartmental model. In total, 49 subjects completed the study. The geometric mean ratio (micronized/conventional) of the maximum concentration and the area under the plasma concentration-time curve from time zero to the last concentration values were 1.08 (90% CI, 0.95-1.24) and 0.97 (90% CI, 0.89-1.05), respectively. The adverse event profile did not differ between the 2 formulations. The results demonstrate that micronized formulation of raloxifene 45 mg is equivalent to conventional formulation of raloxifene 60 mg when administered at the single dose in the fasted state. After single oral dosing of AD-101, there were no serious or unexpected adverse events., (© 2023 The Authors. Clinical Pharmacology in Drug Development published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.)

Background: Although it is known that a substantial proportion of the population experience loneliness, the consequence of loneliness remains unclear by countries and ages. Accordingly, this study aimed to assess the association between loneliness and suicidality in the general population of Korea., Method: A total of 5,511 Koreans aged 18-79 completed a tablet-assisted personal interview using the Korean version of the Composite International Diagnostic Interview and responded to questions about loneliness and lifetime suicidal ideation, plans, and attempts. A logistic regression analysis was used to examine the association between loneliness and suicidality., Results: Approximately one-third of the Korean general population reported loneliness. Being older, never married, widowed, separated, or divorced, unemployed, and having a part-time job were all significantly related to loneliness. After adjusting for sociodemographic factors, individuals with loneliness were significantly associated with increased suicidal ideation (adjusted odd ratio [aOR], 4.05; 95% confidence interval [CI], 3.36-4.88), suicidal plans (aOR, 4.91; 95% CI, 3.34-7.21), and suicidal attempts (aOR, 4.82; 95% CI, 3.03-7.66). Even after adjusting for sociodemographic factors and mental disorders, suicidality remained statistically significant. Moreover, frequent, moderate-to-severe, and long-term loneliness were all associated with increased ORs for suicidality, regardless of sociodemographic factors and mental disorders., Conclusion: Loneliness was associated with suicidal ideation, plans, and attempts. This study lays the foundation for public health policymakers to establish early intervention and mental health care support for lonely people., Competing Interests: This study utilized data of the National Mental Health Survey 2021 (NMHSK-14). The results of this study is irrelevant with the Ministry of Health and Welfare of South Korea. The authors have no potential conflicts of interest to disclose., (© 2023 The Korean Academy of Medical Sciences.)

Objective: The Patient Health Questionnaire-9 (PHQ-9) and PHQ-2 have not been validated in the general Korean population. This study aimed to validate and identify the optimal cutoff scores of the PHQ-9 and PHQ-2 in screening for major depression in the general Korean population., Methods: We used data from 6,022 participants of the Korean Epidemiological Catchment Area Study for Psychiatric Disorders in 2011. Major depression was diagnosed according to the Korean Composite International Diagnostic Interview. Validity, reliability, and receiver operating characteristic curve analyses were performed using the results of the PHQ-9 and Euro Quality of life-5 dimension (EQ-5d)., Results: Of the 6,022 participants, 150 were diagnosed with major depression (2.5%). Both PHQ-9 and PHQ-2 demonstrated relatively high reliability and their scores were highly correlated with the "anxiety/depression" score of the EQ-5d. The optimal cutoff score of the PHQ-9 was 5, with a sensitivity of 89.9%, specificity of 84.1%, positive predictive value (PPV) of 12.6%, negative predictive value (NPV) of 99.7%, positive likelihood ratio (LR+) of 5.6, and negative likelihood ratio (LR-) of 0.12. The optimal cutoff score of the PHQ-2 was 2, with a sensitivity of 85.3%, specificity of 83.2%, PPV of 11.6%, NPV of 99.5%, LR+ of 5.1, and LR- of 0.18., Conclusion: The PHQ-9 and PHQ-2 are valid tools for screening major depression in the general Korean population, with suggested cutoff values of 5 and 2 points, respectively.

This study aimed to demonstrate the feasibility of ureteral navigation using intraoperative indocyanine green (ICG) and near-infrared fluorescence (NIRF) imaging during complex laparoscopic or robot-assisted gynecologic surgery (LRAGS). Twenty-six patients at high risk of ureteral injury with complex pelvic pathology (CPP) due to pelvic organ prolapse (POP), multiple myomas, large intraligamentary or cervical myoma, severe pelvic adhesions, or cervical atresia underwent LRAGS. All patients underwent cystoscopic intraureteral ICG instillation before LRAGS and ureteral navigation under NIRF imaging intraoperatively. Both ureteral pathways were identified from the pelvic brim downwards through NIRF imaging in all patients, even though some were not visualized under the white light mode. The fluorescent ureters were visualized immediately after the beginning of surgery and typically lasted for >5 h during surgery. There were no cases of iatrogenic ureteral injury. The hemoglobin decrement was 1.47 ± 1.13 g/dL, and no transfusion was required. In our study, both ureters in all patients were identified with ICG-NIRF imaging during LRAGS, and these techniques made surgeries easier and safer. Despite the CPP, there was no ureteral injury or transfusion following surgery. Further prospective studies are needed to introduce intraoperative ureteral guidelines for ICG-NIRF imaging during LRAGS with CPP.

Background: The World Health Organization (WHO) proposed a global action plan for dementia and aimed to have 75% of their member states formulating National Dementia Plans (NDPs) by 2025. The Organization for Economic Cooperation and Development (OECD) proposed the ten key objectives of dementia policy in 2015. Among previous studies on NDPs, few studies have investigated measures for proper implementation of NDPs. This study aimed to compare the implementation basis and specific action plans of NDPs between the G7 countries and South Korea., Methods: We investigated the measures for proper implementation of the NDPs of G7 countries and South Korea. To compare the specific policy approaches, the seven action areas of the WHO action plan and the ten key objectives of dementia policy proposed by the OECD were integrated into 11 targets (prevention, diagnosis, awareness, caregiver support, appropriate environments, long-term care, health service, end-of-life care, care coordination, research and technology, information systems)., Results: Although most NDPs included specific action plans of the 11 targets, caregiver support, safe environments, healthcare services, and end-of-life care were lacking in some NDPs. For implementation, some countries reinforced the policy priority of their NDPs by timely updates, evaluation, legislations, or head-of-state leadership. However, only three countries had a legislative basis, and three countries included outcome measures in their latest NDP., Conclusion: Effective measures for feasible implementation are needed. The WHO should promote not only the establishment of NDPs, but also their proper implementation., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2023 The Korean Academy of Medical Sciences.)

Two open-label, randomized, two-period crossover studies were conducted to investigate the pharmacokinetic (PK) properties, safety, and bioequivalence of the test formulation (KD4004), a new fixed-dose combination (FDC) formulation of dapagliflozin and metformin extended release (XR) tablets, relative to the reference formulation (10 mg dapagliflozin/1,000 mg metformin XR FDC tablet) in healthy subjects under fasting (Part A) and fed (Part B) conditions. After giving the dose, serial blood samples were collected for a period of 48 hours. Primary PK parameters (AUC 0-t and C max ) were used to assess bioequivalence between two dapagliflozin/metformin XR (10/1,000 mg) FDC formulations under fed and fasting conditions. Safety and tolerability were also evaluated. Part A and Part B were completed by 32 and 37 subjects, respectively. Bioequivalence of the two FDC formulations of dapagliflozin and metformin XR tablets was established in both the fasted and the fed conditions as the 90% confidence interval of the ratios of adjusted geometric means for AUC 0-t and C max were contained within the predefined range of 0.800-1.250 bioequivalence criteria. Single-dose administration of dapagliflozin and metformin XR was safe and well tolerated as the two FDC formulations. In conclusion, both FDC formulations of dapagliflozin and metformin XR tablets were bioequivalent in fed and fasted subjects. All treatments were well tolerated., Trial Registration: Clinical Research Information Service Identifier: KCT0004026., Competing Interests: Conflict of Interest: - Authors: Nothing to declare - Reviewers: Nothing to declare - Editors: Nothing to declare, (Copyright © 2023 Translational and Clinical Pharmacology.)

Vitamin D is important because it has roles in maintaining musculoskeletal health, redox homeostasis, and the immune system; however, it is commonly dysregulated by endocrine disrupting chemicals, particularly phthalates and bisphenol A (BPA). Continuous exposure to phthalates and BPA may alter the endogenous metabolite profiles associated with vitamin D activity, although the specific metabolites are yet to be identified. In this study, we identified the endogenous metabolites altered by phthalates and BPA exposure through untargeted metabolic profiling and investigated the role of these metabolites in vitamin D activity. Plasma metabolic profiling using liquid chromatography-mass spectrometry was performed in two groups: severe 25-hydroxyvitamin D (25(OH)D) deficiency and high exposure to phthalates and BPA (Group A) and 25(OH)D deficiency and low exposure to phthalates and BPA (Group B). Multivariate analysis revealed a distinct separation between the two groups. A total of six metabolites were annotated, of which levels of two were significantly different between the two groups: platelet-activating factor (PAF) C16 or lysophosphatidylcholine (lysoPC) 18:0, and 11Z-eicosenamide. Plasma levels of PAF C16 or lysoPC 18:0 were increased in Group A and exhibited an area under the curve of 0.769 with an accuracy of 74.4% in a receiver operating characteristic curve analysis. These metabolites are generated as byproducts of lipid peroxidation, which supports the fact that phthalates and BPA induce oxidative stress in cells. Furthermore, PAF C16 and lysoPC 18:0 may be involved in the network that interferes with the antioxidant activity of vitamin D upon exposure to phthalates and BPA. This study results provide useful information on how the activity of vitamin D on the antioxidant system is inhibited when exposure to phthalates and BPA., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: Mental health is a global concern and needs to be studied more closely. We aimed to estimate the prevalence of mental disorders and their associated factors among the general population in Korea., Methods: The National Mental Health Survey of Korea 2021 was conducted between June 19 and August 31, 2021 and included 13,530 households; 5,511 participants completed the interview (response rate: 40.7%). The lifetime and 12-month diagnosis rates of mental disorders were made using the Korean version of the Composite International Diagnostic Interview 2.1. Factors associated with alcohol use disorder (AUD), nicotine use disorder, depressive disorder, and anxiety disorder were analyzed, and mental health service utilization rates were estimated., Results: The lifetime prevalence of mental disorders was 27.8%. The 12-month prevalence rates of alcohol use, nicotine use, depressive, and anxiety disorders were 2.6%, 2.7%, 1.7%, and 3.1%, respectively. The risk factors associated with 12-month diagnosis rates were as follows: AUD: sex and age; nicotine use disorder: sex; depressive disorder: marital status and job status; anxiety disorder: sex, marital status, and job status. The 12-month treatment and service utilization rates for 12-month AUD, nicotine use disorder, depressive disorder, and anxiety disorder were 2.6%, 1.1%, 28.2%, and 9.1%, respectively., Conclusion: Approximately 25% of adults in the general population were diagnosed with mental disorders during their lifetime. The treatment rates were substantially low. Future studies on this topic and efforts to increase the mental health treatment rate at a national level are needed.

Purpose: The aims of this study were to evaluate the cumulative recurrence, reoperation, and pregnancy rates after ovarian endometrioma surgery at a single institution for more than a 5-year follow-up period., Materials and Methods: This study was conducted as a retrospective chart review of patients with ovarian endometrioma who underwent surgery between January 2008 and March 2016. Study subjects included premenopausal women with at least 5 years of follow-up. Exclusion criteria were patients with stage I or II ovarian endometrioma, those who underwent hysterectomy or bilateral oophorectomy, and presence of residual ovarian lesions on the first postoperative ultrasonography at 3-6 months. Recurrence was defined as a cystic mass by ultrasonography., Results: A total of 756 patients were recruited. The median follow-up duration was 85.5 months (interquartile range, 71-107 months). Recurrent endometrioma was detected in 27.9% patients, and reoperation was performed in 8.3% patients. Cumulative rates at 24, 36, 60, and 120 months were 5.8%, 8.7%, 15.5% and 37.6%, respectively, for recurrence and 0.1%, 0.5%, 2.9%, and 15.1%, respectively, for reoperation. After multivariable analysis, age ≤31 years [hazard ratio (HR)=2.108; 95% confidence interval (CI)=1.522-2.921; p <0.001], no subsequent pregnancy (HR=1.851; 95% CI=1.309-2.617; p <0.001), and postoperative hormonal treatment ≤15 months (HR=2.869; 95% CI=2.088-3.941; p <0.001) were significant risk factors for recurrent endometrioma. Among 315 patients who desired pregnancy, 54.0% were able to have a successful pregnancy and delivery., Conclusion: Considering that longer postoperative hormonal treatment is the sole modifiable factor for recurrent endometrioma, we recommend long-term hormonal treatment until subsequent pregnancy, especially in younger women., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2023.)

Objective: The aim of this study was to determine whether robotic myomectomy (RM) resulted in any measurable clinical improvement over laparoscopic myomectomy (LM) in subsequent cesarean delivery., Materials and Methods: The medical records of 273 patients who had undergone LM or RM followed by subsequent cesarean delivery for the period of September 2015 to December 2020 were retrospectively reviewed. The patients were divided into LM (n = 222) and RM (n = 51) groups. The cesarean delivery outcomes between the two groups were compared., Results: RM had significantly more myomas removed (6.0 ± 4.8 vs. 3.6 ± 3.5, p < 0.001) and a larger size of largest myoma (7.7 ± 2.4 vs. 6.1 ± 2.4, p = 0.002) at myomectomy compared with LM. However, there were no significant differences in the groups' surgical characteristics at cesarean section, in their pregnancy complications, or in adhesion formation., Conclusions: Although more and larger myomas were removed in the RM group, RM showed similar cesarean delivery outcomes and adhesion formation to LM., Competing Interests: Declaration of Competing Interest There are no conflicts of interest to declare., (Copyright © 2023. Published by Elsevier B.V.)

Background: There is still concern regarding postoperative adhesion formation and adverse effects on pregnancy outcomes caused by barbed suture (BS) after myomectomy. The aim of this study was to compare the postoperative adhesion and pregnancy outcomes between conventional suture (CS) and BS after minimally invasive myomectomy (MIM) by robotic myomectomy (RM) or laparoscopic myomectomy (LM). Methods: The medical records of 94 women who had undergone MIM with CS and 97 who had undergone MIM with BS and achieved pregnancy were reviewed. Postoperative adhesion was evaluated following cesarean section. Results: The number of removed myomas was greater (5.3 ± 4.6 vs. 3.5 ± 3.1, p = 0.001) and the size of the largest myoma was larger (7.0 ± 2.2 vs. 5.8 ± 2.7 cm, p = 0.001) in the BS group relative to the CS group. A total of 98.9% of patients in the CS group and 45.4% in the BS group had undergone LM (p < 0.001), while the others underwent RM. There was no significant difference in the presence of postoperative adhesion at cesarean section between the BS and CS groups (45.5 vs. 43.7%, p = 0.095). Additionally, there were no intergroup differences in pregnancy complications such as preterm labor, placenta previa, accrete or abruption. Note also that in our logistic regression analysis, the suture type (BS or CS) was excluded from the independent risk factors regarding postoperative adhesion formation. Conclusions: Our data indicated that the incidence of postoperative adhesion after MIM with BS was similar when compared with CS. Also it seems that the suture type does not have a significant effect on pregnancy outcomes.

Background: The aim of this study was to introduce a coaxial-robotic single-site myomectomy (C-RSSM) technique to compensate for the shortcomings of robotic single-site myomectomy (RSSM) using semi-rigid instruments and to compare the surgical outcomes of C-RSSM and RSSM., Methods: The medical records of 13 consecutive women who had undergone C-RSSM and 131 consecutive women who had undergone RSSM were retrospectively reviewed. Patient characteristics and surgical outcomes after propensity score matching were evaluated and compared between the two groups., Results: According to the propensity score matching results, the C-RSSM group had a lower estimated blood loss (75.0 vs. 210.5 mL, p = 0.001) and a shorter operating time (101.0 vs. 146.1 min, p = 0.008) relative to the RSSM group. In RSSM, there was one case of conversion to conventional laparoscopy and four cases of conversion to the multi-site robotic approach. There was no case of conversion from C-RSSM to conventional laparoscopy or the multi-site robotic approach., Conclusions: C-RSSM was found to be associated with shorter operative time and lower estimated blood loss. However, further prospective studies are needed to confirm these advantages.

We aimed to evaluate the clinical impact of shift patterns at work on gynecologic problems and the healthcare behavior of Korean nursing staff. We conducted a web-based survey for over two weeks in September 2021, involving female nursing staff, including nurses, nurses' aides, and nursing assistants, working in five medical centers. The questionnaire included 40 questions on baseline characteristics, working information, and experiences with gynecologic problems and medical approaches. Overall, 885 nursing staffs participated in the survey, of the 1,904 who received the invitation with an online link of the survey. The response rate was 46.5%. Among the participants responding to all questions, 569 (64.4%) worked two or three shifts and 305 (34.5%) worked full-time. In women rotating two or three-shift patterns, irregular menstrual cycles (21.6% vs. 13.8%, p = 0.005), abnormal menstrual cycles (40.9% vs. 33.8%, p = 0.038), and dysmenorrhea (48.0% vs. 38.4%, p = 0.006) were more frequent than in those who worked full-time. The experience of visiting gynecologic clinics (47.5% vs. 44.1%, p = 0.332) and treating gynecologic conditions (33.4% vs. 29.3%, p = 0.211) did not differ according to the working patterns. However, diagnosis of gynecologic diseases was more frequent in women working full-time (36.4% vs. 29.7%, p = 0.043). The rates of screening (76.1% vs. 57.8%, p<0.001) and human papillomavirus vaccination (55.7% vs. 39.9%, p<0.001) for cervical cancer prevention were higher in women working full-time than in two-three shifts. This study showed that rotating shift work may be related to an increase in gynecologic problems and a decrease in cancer prevention activity among female nursing staff., Competing Interests: The authors have declared that no competing interests exist.

A new fixed-dose combination (FDC) formulation of raloxifene 60 mg and cholecalciferol 800 IU was developed to improve the medication compliance and overall efficacy of raloxifene treatment in postmenopausal osteoporosis patients. The aim of this study was to compare the pharmacokinetics between two tablets of FDC formulation of raloxifene/cholecalciferol and the two products administered concomitantly at respective doses. This randomized, open-label, single-dose, two-treatment, two-way crossover study included 46 volunteers. During each treatment period, subjects received the test formulation (FDC formulation containing raloxifene and cholecalciferol) or the reference formulation (co-administration of raloxifene and cholecalciferol), with a 14-d washout period. Serial blood samples were collected periodically over 96 hours after drug intake. In total, 46 subjects completed the study. The geometric mean ratios and its 90% confidence intervals of the FDC to the single agents for the area under the concentration-time curve from zero to the last quantifiable time point and the maximum plasma concentration met the regulatory criteria for bioequivalence: 1.1364 (1.0584-1.2201) and 1.1010 (0.9945-1.2188) for raloxifene and 1.0266 (0.9591-1.0989) and 1.0354 (0.9816-1.0921) for baseline-corrected cholecalciferol, respectively. Both formulations were well tolerated. No significant differences was observed in the incidence of adverse events between the two treatments. It was concluded that two tablets of the newly developed FDC formulation of raloxifene and cholecalciferol and the corresponding two agents administered concomitantly at respective doses were bioequivalent., Trial Registration: ClinicalTrials.gov Identifier: NCT03010267., Competing Interests: Conflict of Interest: B. L. is an employee of Alvogen Korea Co. Ltd. The authors have indicated that they have no other conflicts of interest regarding the content of this article. The sponsor did not participate in the execution of the study or analysis of the data., (Copyright © 2022 Translational and Clinical Pharmacology.)

Background: Robotic single-site plus two port myomectomy (RSTM) was designed to reduce the number of incision sites while retaining the advantage of conventional robotic multi-port myomectomy (CRM). This study aimed to explicate RSTM and compare surgical outcomes between it and CRM. Methods: The medical records of 146 patients who had undergone RSTM and 173 who had undergone CRM were reviewed. The surgical outcomes between them were compared by propensity score matching (PSM) analysis. Results: The PSM analysis showed no statistically significant inter-group differences in patient characteristics. With regard to surgical outcomes, the RSTM group enjoyed shorter operative time (148.30 ± 44.8 vs. 162.3 ± 47.4 min, p = 0.011), less hemoglobin decrement (1.8 ± 0.9 vs. 2.3 ± 1.0 g/dL, p < 0.001), and shorter duration of hospital stay (5.4 ± 0.7 vs. 5.8 ± 0.7 days, p < 0.001). Conclusions: RSTM was associated with shorter operative time relative to CRM. Further prospective studies are needed in order to more fully investigate the advantages of RSTM.

Although wearable electrocardiograms (ECGs) are being increasingly applied in clinical settings, validation methods have not been standardized. As an exploratory evaluation, we performed a multicenter clinical trial implementing an approved wearable patch ECG. Healthy male adults were enrolled in 2 study centers. The approved ECGs were deployed for 6 hours, and pulse rates were measured independently with conventional pulse oximetry at selected time points for correlation analyses. The transmission status of the data was evaluated by heart rates and classified into valid, invalid, and missing. A total of 55 subjects (40 in center 1 and 15 in center 2) completed the study. Overall, 77.40% of heart rates were within the valid range. Invalid and missing data accounted for 1.42% and 21.23%, respectively. There were significant differences in valid and missing data between centers. The proportion of missing data in center 1 (24.77%) was more than twice center 2 (11.77%). Heart rates measured by the wearable ECG and conventional pulse oximetry showed a poor correlation (intraclass correlation coefficient = 0.0454). In conclusion, we evaluated the multicenter feasibility of implementing wearable ECGs. The results suggest that systems to mitigate multicenter discrepancies and remove artifacts should be implemented prior to performing a clinical trial., Trial Registration: ClinicalTrials.gov Identifier: NCT05182684., Competing Interests: Conflict of Interest: - Authors: Nothing to declare - Reviewers: Nothing to declare - Editors: Nothing to declare, (Copyright © 2022 Translational and Clinical Pharmacology.)

Purpose: This study aimed to evaluate the cumulative recurrence rate and risk factors for recurrent abdominal wall endometriosis (AWE) after surgical treatment., Materials and Methods: A retrospective cohort study was conducted at a single gynecological surgery center between January 2004 and December 2020. Patients who were surgically treated and followed up for at least 6 months after surgery were selected., Results: Eighteen patients with pathologically diagnosed AWE were included in this study. The median follow-up duration was 22.5 months (range, 6-106). The median age was 37 years (range, 22-48), and 33.3% of the patients were nulliparous. Among the patients included in our study, 55.6% complained of a mass with cyclic pain, and 27.8% had a palpable mass. In addition, 22.2% of patients experienced recurrence with 17.5±9.7 months of mean time to recurrence. The cumulative recurrence rates at 24 and 60 months after surgical treatment of AWE were 23.8% and 39.1%, respectively. There were no statistically significant risk factors for the recurrence of AWE, including postoperative medical treatment., Conclusion: The recurrence rate of AWE appears to be correlated with the follow-up duration. There was no statistically significant risk factor for the recurrence of AWE. Unlike ovarian endometriosis, postoperative hormonal treatment does not seem to lower the recurrence of AWE. The findings of the current study may help healthcare providers in counselling and managing patients with AWE., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2022.)

Osteoporosis is a common skeletal disorder, often leading to fragility fracture. Combination therapy with raloxifene, a selective estrogen receptor modulator, and cholecalciferol (vitamin D 3 ) has been proposed to improve the overall efficacy and increase compliance of raloxifene therapy for postmenopausal osteoporosis. To our knowledge, there has been no report of any study on the pharmacokinetic interaction between raloxifene and cholecalciferol. This study aimed to evaluate the possible pharmacokinetic interactions between raloxifene and cholecalciferol in healthy adult male Korean volunteers. Twenty subjects completed this open-label, randomized, single-dose, 3-period, 6-sequence, crossover phase 1 study with a 14-day washout period. Serial blood samples were collected from 20 hours before dosing to 96 hours after dosing. The plasma concentrations of raloxifene and cholecalciferol were determined using a validated method for high-performance liquid chromatography with tandem mass spectrometry. The geometric mean ratios (90%CIs) for area under the plasma concentration-time curve from time 0 to the last quantifiable time point and maximum plasma concentration of raloxifene with or without cholecalciferol were 1.02 (0.87-1.20) and 0.87 (0.70-1.08), respectively. For baseline-corrected cholecalciferol, geometric mean ratios (90%CIs) of area under the plasma concentration-time curve from time 0 to the last quantifiable time point and maximum plasma concentration with or without raloxifene were 1.01 (0.93-1.09) and 0.99 (0.92-1.06), respectively. Concurrent treatment with raloxifene and cholecalciferol was generally well tolerated. These results suggest that raloxifene and cholecalciferol have no clinically relevant pharmacokinetic drug-drug interactions when administered concurrently. All treatments were well tolerated, with no serious adverse events., (© 2022 The Authors. Clinical Pharmacology in Drug Development published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.)

Background: Ovarian "seromucinous carcinoma" has been recently removed in 2020 5 th Edition of WHO classification of Female Genital Tumors and is considered as a subtype of endometrioid carcinoma with mucinous differentiation, while "seromucinous borderline tumor" remains and exists as a distinct entity. Both diseases may be considered as no more same lineage. However, ovarian seromucinous borderline tumor (SMBT) is also one of the endometriosis-related neoplasm of ovary similar to endometrioid tumor, featuring that about 50% of ovarian SMBTs combine endometriosis. The present study was aimed to investigate whether the ovarian SMBTs are different in clinical features and molecular patterns, according to the presence of combined endometriosis., Results: There were no statistical differences in clinical findings between two groups. There was also no significant difference in pregnancy outcomes and recurrence between two groups. In immunohistochemical patterns, there was a statistically significant difference in PAX2 and PAX8 expression between in ovarian SMBT with or without endometriosis (P = 0.016, P < 0.001). Only a few cases of ovarian SMBT with endometriosis showed expression of PAX2 and conversely, most of the cases showed expression of PAX8. PR positivity was more prominent in ovarian SMBT with endometriosis than without endometriosis (P = 0.018), although there was no difference in positive ER expression. There were no statistical differences in WT1, CK20 and CDX2 expressions between two groups., Conclusions: Ovarian SMBT with endometriosis did not clinically differ from that without endometriosis. However, the molecular patterns were different between two groups and ovarian SMBT with endometriosis is close to endometrioid tumor types unlike SMBT without endometriosis. Further, a direct comparison study between seromucinous borderline tumor and endometrioid borderline tumor is needed with a gene profiling study to prove their relationship., (© 2022. The Author(s).)